N-linked glycosylation is a common protein modification found on many secreted and membrane-bound glycoproteins. The synthesis of complex glycoforms requires a series of enzymatic reactions carried out in a step-wise manner in the endoplasmic reticulum and Golgi apparatus of eukaryotic cells. While the majority of recombinant therapeutic proteins require the presence of complex glycans to avoid immunogenicity and to improve protein half-life, applications for glycoproteins with simple N-glycan structures also exist. For example, recombinant proteins with simple glycoforms are advantageous for X-ray crystallography studies. Additionally, simple glycoforms with only terminal mannose residues can lead to increased efficacy of some therapeutics by facilitating mannose receptor-mediated uptake for these proteins.
Most cell lines used for the production of therapeutic glycoproteins produce proteins with heterogeneous or complex N-linked glycoforms, however. Thus, there is a need for cell lines that are engineered to produce recombinant glycoproteins with simple glycoforms. Moreover, it is desirable that these engineered cell lines stably produce proteins with terminal mannose residues, while retaining high protein productivity and robust growth in chemically-defined culture media.